Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

Paper-based microfluidics for DNA diagnostics of malaria in low resource underserved rural communities

Rapid, low-cost, species-specific diagnosis, based upon DNA testing, is becoming important in the treatment of patients with infectious diseases. Here, we demonstrate an innovation that uses origami to enable multiplexed, sensitive assays that rival polymerase chain reactions (PCR) laboratory assays and provide high-quality, fast precision diagnostics for malaria. The paper-based microfluidic technology proposed here combines vertical flow sample-processing steps, including paper folding for whole-blood sample preparation, with an isothermal amplification and a lateral flow detection, incorporating a simple visualization system. Studies were performed in village schools in Uganda with individual diagnoses being completed in <50 min (faster than the standard laboratory-based PCR). The tests, which enabled the diagnosis of malaria species in patients from a finger prick of whole blood, were both highly sensitive and specific, detecting malaria in 98% of infected individuals in a double-blind first-in-human study. Our method was more sensitive than other field-based, benchmark techniques, including optical microscopy and industry standard rapid immunodiagnostic tests, both performed by experienced local healthcare teams (which detected malaria in 86% and 83% of cases, respectively). All assays were independently validated using a real-time double-blinded reference PCR assay. We not only demonstrate that advanced, low-cost DNA-based sensors can be implemented in underserved communities at the point of need but also highlight the challenges associated with developing and implementing new diagnostic technologies in the field, without access to laboratories or infrastructure

The impact of ENSO on Southern African rainfall in CMIP5 ocean atmosphere coupled climate models

We study the ability of 24 ocean atmosphere global coupled models from the Coupled Model Intercomparison Project 5 (CMIP5) to reproduce the teleconnections between El Niño Southern Oscillation (ENSO) and Southern African rainfall in austral summer using historical forced simulations, with a focus on the atmospheric dynamic associated with El Niño. Overestimations of summer rainfall occur over Southern Africa in all CMIP5 models. Abnormal westward extensions of ENSO patterns are a common feature of all CMIP5 models, while the warming of the Indian Ocean that happens during El Niño is not correctly reproduced. This could impact the teleconnection between ENSO and Southern African rainfall which is represented with mixed success in CMIP5 models. Large-scale anomalies of suppressed deep-convection over the tropical maritime continent and enhanced convection from the central to eastern Pacific are correctly simulated. However, regional biases occur above Africa and the Indian Ocean, particularly in the position of the deep convection anomalies associated with El Niño, which can lead to the wrong sign in rainfall anomalies in the northwest part of South Africa. From the near-surface to mid-troposphere, CMIP5 models underestimate the observed anomalous pattern of pressure occurring over Southern Africa that leads to dry conditions during El Niño years

Understanding the rapid summer warming and changes in temperature extremes since the mid-1990s over Western Europe

Analysis of observations indicates that there was a rapid increase in summer (June-August, JJA) mean surface air temperature (SAT) since the mid-1990s over Western Europe. Accompanying this rapid warming are significant increases in summer mean daily maximum temperature, daily minimum temperature, annual hottest day temperature and warmest night temperature, and an increase in frequency of summer days and tropical nights, while the change in the diurnal temperature range (DTR) is small. This study focuses on understanding causes of the rapid summer warming and associated temperature extreme changes. A set of experiments using the atmospheric component of the state-of-the-art HadGEM3 global climate model have been carried out to quantify relative roles of changes in sea surface temperature (SST)/sea ice extent (SIE), anthropogenic greenhouse gases (GHGs), and anthropogenic aerosols (AAer). Results indicate that the model forced by changes in all forcings reproduces many of the observed changes since the mid-1990s over Western Europe. Changes in SST/SIE explain 62.2% ± 13.0% of the area averaged seasonal mean warming signal over Western Europe, with the remaining 37.8% ± 13.6% of the warming explained by the direct impact of changes in GHGs and AAer. Results further indicate that the direct impact of the reduction of AAer precursor emissions over Europe, mainly through aerosol-radiation interaction with additional contributions from aerosol-cloud interaction and coupled atmosphere-land surface feedbacks, is a key factor for increases in annual hottest day temperature and in frequency of summer days. It explains 45.5% ± 17.6% and 40.9% ± 18.4% of area averaged signals for these temperature extremes. The direct impact of the reduction of AAer precursor emissions over Europe acts to increase DTR locally, but the change in DTR is countered by the direct impact of GHGs forcing. In the next few decades, greenhouse gas concentrations will continue to rise and AAer precursor emissions over Europe and North America will continue to decline. Our results suggest that the changes in summer seasonal mean SAT and temperature extremes over Western Europe since the mid-1990s are most likely to be sustained or amplified in the near term, unless other factors intervene

TLR7 ligation augments hematopoiesis in Rps14 (uS11) deficiency via paradoxical suppression of inflammatory signaling

Myelodysplastic syndrome (MDS) is a hematological malignancy characterized by blood cytopenias and predisposition to acute myeloid leukemia (AML). Therapies for MDS are lacking, particularly those that have an impact in the early stages of disease. We developed a model of MDS in zebrafish with knockout of Rps14, the primary mediator of the anemia associated with del(5q) MDS. These mutant animals display dose- and age-dependent abnormalities in hematopoiesis, culminating in bone marrow failure with dysplastic features. We used Rps14 knockdown to undertake an in vivo small-molecule screening, to identify compounds that ameliorate the MDS phenotype, and we identified imiquimod, an agonist of Toll-like receptor-7 (TLR7) and TLR8. Imiquimod alleviates anemia by promoting hematopoietic stem and progenitor cell expansion and erythroid differentiation, the mechanism of which is dependent on TLR7 ligation and Myd88. TLR7 activation in this setting paradoxically promoted an anti-inflammatory gene signature, indicating cross talk via TLR7 between proinflammatory pathways endogenous to Rps14 loss and the NF-κB pathway. Finally, in highly purified human bone marrow samples from anemic patients, imiquimod led to an increase in erythroid output from myeloerythroid progenitors and common myeloid progenitors. Our findings have both specific implications for the development of targeted therapeutics for del(5q) MDS and wider significance identifying a potential role for TLR7 ligation in modifying anemia

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Identifying Topological Order by Entanglement Entropy

Topological phases are unique states of matter incorporating long-range quantum entanglement, hosting exotic excitations with fractional quantum statistics. We report a practical method to identify topological phases in arbitrary realistic models by accurately calculating the Topological Entanglement Entropy (TEE) using the Density Matrix Renormalization Group (DMRG). We argue that the DMRG algorithm naturally produces a minimally entangled state, from amongst the quasi-degenerate ground states in a topological phase. This proposal both explains the success of this method, and the absence of ground state degeneracy found in prior DMRG sightings of topological phases. We demonstrate the effectiveness of the calculational procedure by obtaining the TEE for several microscopic models, with an accuracy of order $10^{-3}$ when the circumference of the cylinder is around ten times the correlation length. As an example, we definitively show the ground state of the quantum $S=1/2$ antiferromagnet on the kagom\'e lattice is a topological spin liquid, and strongly constrain the full identification of this phase of matter.Comment: 20 pages, 6 figure

Informing the development of an online self-management program for men living with HIV: a needs assessment

Background: The aim of this mixed methods study was to conduct a multifaceted needs assessment to inform the development of an online self-management program for men living with HIV. The objectives were to describe the health-related quality of life for men living with HIV, the impact of living with HIV, and the perceived problem areas and service and support needs of these men. The needs assessment was conducted in accordance with the PRECEDE model for health promotion program planning.Methods: A survey assessing the quality of life of men living with HIV (n = 72) was conducted and results were compared to Australian normative data. Focus groups were also undertaken with men living with HIV (n = 11) and a multidisciplinary team of service providers working in the area of HIV (n = 11). Focus groups enabled an in-depth description of the impact of HIV on quality of life and perceived problem areas in daily life.Results: HIV-positive men experience significantly lower quality of life when compared with Australian normative data, particularly in those domains concerned with social and emotional aspects of quality of life. Qualitative focus groups yielded an overarching theme ‘The psychosocial impact of HIV’ which contained three sub-themes; (1) Life before and after HIV – a changed identity and its repercussions; (2) Resilience and the importance of social support; (3) Negotiating the practicalities – intimate relationships and disclosure.Conclusions: The findings from this needs assessment highlight the need to target socio-emotional contexts of HIV positive men’s daily lives to improve quality of life and well-being. Intervention priorities for the proposed online self-management program include: (1) managing the emotional impact of HIV; (2) disclosing HIV status to family and friends; (3) maintaining social connectedness; (4) managing HIV within intimate relationships; and (5) disclosure of HIV status to intimate partners

Physiological aspects of the determination of comprehensive arterial inflows in the lower abdomen assessed by Doppler ultrasound

Non-invasive measurement of splanchnic hemodynamics has been utilized in the clinical setting for diagnosis of gastro-intestinal disease, and for determining reserve blood flow (BF) distribution. However, previous studies that measured BF in a "single vessel with small size volume", such as the superior mesenteric and coeliac arteries, were concerned solely with the target organ in the gastrointestinal area, and therefore evaluation of alterations in these single arterial BFs under various states was sometimes limited to "small blood volumes", even though there was a relatively large change in flow. BF in the lower abdomen (BFAb) is potentially a useful indicator of the influence of comprehensive BF redistribution in cardiovascular and hepato-gastrointestinal disease, in the postprandial period, and in relation to physical exercise. BFAb can be determined theoretically using Doppler ultrasound by subtracting BF in the bilateral proximal femoral arteries (FAs) from BF in the upper abdominal aorta (Ao) above the coeliac trunk. Prior to acceptance of this method of determining a true BFAb value, it is necessary to obtain validated normal physiological data that represent the hemodynamic relationship between the three arteries. In determining BFAb, relative reliability was acceptably high (range in intra-class correlation coefficient: 0.85-0.97) for three arterial hemodynamic parameters (blood velocity, vessel diameter, and BF) in three repeated measurements obtained over three different days. Bland-Altman analysis of the three repeated measurements revealed that day-to-day physiological variation (potentially including measurement error) was within the acceptable minimum range (95% of confidence interval), calculated as the difference in hemodynamics between two measurements. Mean BF (ml/min) was 2951 ± 767 in Ao, 316 ± 97 in left FA, 313 ± 83 in right FA, and 2323 ± 703 in BFAb, which is in agreement with a previous study that measured the sum of BF in the major part of the coeliac, mesenteric, and renal arteries. This review presents the methodological concept that underlies BFAb, and aspects of its day-to-day relative reliability in terms of the hemodynamics of the three target arteries, relationship with body surface area, respiratory effects, and potential clinical usefulness and application, in relation to data previously reported in original dedicated research